Disposable cassette for intravascular heat exchange catheter

ABSTRACT

A heat exchange fluid supply system for supplying a heat exchange fluid to an intravascular heat exchange catheter includes a disposable cassette having a bulkhead and an external heat exchanger, and which is configured to operate in combination with a reusable master control unit The bulkhead includes a reservoir section and a pump section. The reservoir section is provided with a means to monitor the amount of heat exchange fluid that is in the system. The bulkhead provides the mechanism for priming the system with heat exchange fluid from an external source and for circulating fluid to the catheter in a closed circuit. The pump section is configured to allow for pumping of heat exchange fluid at a constant pressure.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. Ser. No. 09/563,946, filedMay 2, 2000, now U.S. Pat. No. 6,673,098, which is acontinuation-in-part of U.S. Ser. No. 09/138,830, filed Aug. 24, 1998,now U.S. Pat. No. 6,620,188, an which claims benefit of 60/185,561,filed Feb. 28, 2000.

TECHNICAL FIELD

The present invention is directed to a fluid supply and fluid handlingmechanism for an intravascular heat exchanger, and more particularly toa disposable cassette with a pump head and an external heat exchangerfor use as a system to provide hot or cold heat transfer fluid to anintravascular heat exchange catheter.

BACKGROUND

Under ordinary circumstances, thermoregulatory mechanisms exist in thehealthy human body to maintain the body at a constant temperature ofabout 37° C. (98.6° F.), a condition sometimes referred to asnormothermia. To maintain normothermia, the thermoregulatory mechanismsact so that heat lost to the environment is replaced by the same amountof heat generated by metabolic activity in the body.

For various reasons, however, a person may accidentally develop a bodytemperature that is above or below normal, conditions known ashyperthermia or hypothermia respectively. These conditions havegenerally been regarded as harmful and patients suffering from eithercondition have been treated to return them to normothermia by variousmechanisms, including application of warming or cooling blankets,administration of hot or cold liquids by mouth, hot or cold liquidsinfused into the bloodstream, immersion of the patient in hot or coldbaths, and directly heating or cooling blood during cardiopulmonarybypass.

Besides treating undesirable hypothermia to reverse the condition andrestore normothermia, medical science recognizes that it is sometimesvaluable to intentionally induce and maintain regional or whole bodyhypothermia for therapeutic reasons. The term “whole body hypothermia”refers to the condition where the whole body temperature, usuallymeasured as the core body temperature, is below normothermia. “Regionalhypothermia” refers to the condition where target tissue of one regionof the body such as the brain or the heart is maintained at atemperature below normothermia. During regional hypothermia, the corebody temperature may be normothermic, or may be slightly hypothermic butis generally warmer than the target tissue.

It may be desirable, for example, to induce whole body or regionalhypothermia for the purpose of treating, or minimizing the adverseeffects of, certain neurological diseases or disorders such as headtrauma, spinal trauma and hemorrhagic or ischemic stroke. Additionally,it is sometimes desirable to induce whole body or regional hypothermiafor the purpose of facilitating or minimizing adverse effects of certainsurgical or interventional procedures such as open heart surgery,aneurysm repair surgeries, endovascular aneurysm repair procedures,spinal surgeries, or other surgeries where blood flow to the brain,spinal cord or vital organs may be interrupted or compromised. Neuraltissue such as the brain or spinal cord, is particularly subject todamage by blood deprivation for any reason including ischemic orhemorrhagic stroke, cardiac arrest, intracerebral or intracranialhemorrhage, and head trauma In each of these instances, damage to braintissue may occur because of brain ischemia, increased intracranialpressure, edema or other processes, often resulting in a loss ofcerebral function and permanent neurological deficits. Hypothermia hasalso been found to be advantageous to protect cardiac muscle tissueduring or after ischemia, for example during heart surgery or during orafter a myocardial infarct.

Traditional methods inducing and/or maintaining hypothermia includeapplication of surface cooling such as an ice bath or cooling blankets,infusing cold liquid into the vascular system of a patient, orcontrolling the temperature of a patient's blood during cardiopulmonarybypass. While each of these may be useful in certain settings, they eachhave significant disadvantages. For example, inducing hypothermia byplacing a patient into a cold bath lacks precise control over apatient's core temperature and thus may result in harmful overshoot,which may be difficult if not impossible to reverse with any degree ofcontrol. It generally cannot be used in conjunction with surgery becausesterility and access to the patient's body may make its use impracticalor impossible. Cooling blankets are often too slow to cool the patient,or simply unable to overcome the body's natural ability to generateheat, particularly if the patient is shivering or experiencingvasoconstriction. Even if the patient is anesthetized, or has otherwisehad his thermoregulatory responses impaired or eliminated, cooling bymeans of cooling blankets is still often too slow and inefficient to beuseful. Control over the patient's temperature is generally poor, whichis particularly dangerous if the patient's own thermoregulatory controlsare eliminated or impaired.

Infusion of cold or hot fluid into a patient's bloodstream has also beenused to affect the temperature of a patient. However, this procedure isseverely limited because of the hazards of fluid loading. Particularlywhere hypothermia is to be maintained for a long period of time,continuous infusion of sufficient cold liquid to counter the heatgenerated by ordinary bodily activity creates an unacceptable amount offluid introduced into the body. In addition, as with the methodsdescribed above, control over the patient temperature is limited.

Another method sometimes employed, especially during heart surgery, iscardiopulmonary bypass, where blood is removed from the body, oxygenatedand returned to the circulatory system by means of a mechanical pump.While being circulated outside the body, the temperature of the bloodmay be controlled by directly heating or cooling it and then pumping itback into the body, and in this way the temperature of the entire bodyof the patient may be controlled. Because of the large volume of bloodremoved, treated, and pumped back into the body, heating or cooling thebody by means of cardiopulmonary bypass is very rapid and may beprecisely controlled. However, the use of an external mechanical pump tocirculate blood tends to be very destructive of the blood and thusphysicians try to minimize the time on which the blood is beingsubjected to this treatment, preferably to four hours or less.Furthermore, the situations in which the use of this method fortemperature control is very limited because of the extremely invasivenature of cardiopulmonary bypass. The patient must be anesthetized,highly trained personnel are required, and the procedure is onlyavailable in an operating room or similarly equipped facility.

Intravascular heat exchangers have been developed to control patienttemperature for either treating hypothermia or hyperthermia or inducingand maintaining hypothermia The intravascular heat exchanger overcomesmany of the shortcomings of the above mentioned methods while permittingthe advantageous aspects of controlling patient temperature. Theintravascular heat exchanger comprises a catheter in which heat transferfluid is circulated between an external heat exchanger, such as a solidstate thermoelectric plate of one or more Peltier cooling units and aheat transfer region such as a balloon region on the end of thecatheter. The heat exchange region is inserted into the vasculature of apatient. The heat transfer fluid exchanges heat with the blood at theheat transfer region to change the temperature of the blood and thus ofthe patient. The heat transfer fluid is then circulated out of the bodyand exchanges heat with the external heat exchanger outside the body toadd or remove the heat lost or gained from the blood. In this manner thetemperature of the blood and ultimately of the patient may be controlledby controlling the temperature of the external heat exchanger.

Some intravascular heat exchange catheters may be designed to affect asmall amount of tissue, for example a small bolus of blood inthermodilution catheters (see e.g. Williams, U.S. Pat. No. 4,941,475) orcatheters designed to protect or affect the tissue in contact with thecatheter (see e.g. Neilson, et al., U.S. Pat. No. 5,733,319). However,intravascular heat exchangers designed to affect whole or regional bodytemperature may be expected to exchange a significant amount of energy,for example more than 100 watts. This is achieved by maintaining amaximum difference in temperature between the blood and the heattransfer region (ΔT), and flowing a maximum amount of heat exchangefluid through the circuit. A heat exchange fluid that can be maintainedbetween 0° C. and 45° C. is generally preferable, along with a fluidsupply system that can supply adequate flow of heat transfer fluid andtemperature control of that fluid. Such systems ideally will also haveone of more of the following properties: maximum external heat exchangeability, closed circuit for sterility, small volume for precise andrapid control of temperature, a system for pressure regulation toprecisely control flow rate, optimal flow rate, disposable features,ease of handling, and reliability.

SUMMARY OF THE INVENTION

One aspect of the invention is a heat exchange fluid supply system forsupplying a heat exchange fluid to an intravascular heat exchangecatheter, which includes a disposable cassette having a pump head and anexternal heat exchanger. The configuration of the external heatexchanger is not intended to be structurally limited and may include asack-like configuration, a relatively flat configuration with multiplepaths therein, with a long serpentine path therein, or any othersuitable configuration capable of mating with a heat generating orremoving unit. The system may be configured to operate in combinationwith a reusable master control unit and an external fluid source.

Another aspect of the invention is a disposable cassette for supplying aheat exchange fluid to a heat exchange catheter, the cassettecomprising: an external heat exchanger comprising a flow channel havingan inlet and an outlet; a first fluid supply line, the first fluidsupply line being in fluid communication with the flow channel inlet; apump head contained in the disposable fluid supply cassette, and havinga pump inlet and a pump outlet, where the pump inlet is in fluidcommunication with the external heat exchanger flow channel outlet forpumping fluid from the external heat exchanger flow channel outlet; asecond fluid supply line, the second fluid supply line being in fluidcommunication with the pump outlet for receiving fluid pumped out of thepump outlet; and a pressure regulator, the pressure regulator being influid communication with the pump outlet for regulating the pressure offluid pumped from the pump head.

Yet another aspect of the invention is a heat exchange fluid supplysystem for a heat exchange catheter, the system comprising: an externalheat exchanger comprising a structural member and a compliant member,where the compliant member is sealed to the structural member in apattern, the pattern forming a flow channel between the compliant memberand the structural member, and the flow channel having an inlet and anoutlet; a first fluid supply line, the first fluid supply line being influid communication with the flow channel inlet; a bulkhead, thebulkhead comprising a pump head and a reservoir, the reservoir having areservoir inlet and a reservoir outlet, the reservoir inlet being influid communication with the external heat exchanger flow channeloutlet, the pump head having a pump inlet and a pump outlet, the pumpinlet being in fluid communication with the reservoir outlet for pumpingfluid from the reservoir outlet; a second fluid supply line, the secondfluid supply line being in fluid communication with the pump outlet forreceiving fluid pumped out of the pump outlet; and an external fluidsource, the external fluid source being in fluid communication with thebulkhead.

Still another aspect of the invention is a disposable cassette forsupplying heat exchange fluid to a heat exchange catheter, the cassettecomprising: an external heat exchanger having an inlet and an outlet; afirst fluid supply line, the first fluid supply line in fluidcommunication with the heat exchanger inlet; a disposable pump headcontained in the cassette, the pump head actuated by an electric motor,the pump head having an inlet and an outlet, and the pump inlet being influid communication with the heat exchanger outlet; a second fluidsupply line, the second fluid supply line being in fluid communicationwith the pump outlet for receiving fluid pumped out of the pump outlet;and an optional pressure regulator, the pressure regulator being influid communication with the pump outlet for regulating the pressure offluid pumped from said pump head.

Another aspect of the invention is a disposable cassette for supplying aheat exchange fluid to an intravascular heat exchange catheter, thecassette having a bulkhead and an external heat exchanger. The externalheat exchanger has a thin heat exchanger layer and a back plate fusedtogether to form a serpentine flow channel or a plurality of flowchannels, and has an inlet orifice and an outlet orifice that allowfluid to circulate through the external heat exchanger and whichcommunicate with the bulkhead. In one embodiment, the bulkhead has threecomponents which can be independent sections coupled together or whereat least two of the sections are housed together: a reservoir section, afeedblock section and a pump section. The reservoir section has an inlethole leading from the external heat exchanger and an outlet leading tothe feedblock section, a fluid reservoir for storage of heat exchangefluid, a fluid level detector for monitoring the level of heat exchangefluid within the fluid reservoir, a cover plate that functions to retainfluid within the reservoir and which is fitted with at least one venthole into which is positioned a hydrophobic vent for releasing aircontained within the fluid reservoir. The feedblock section has acentral chamber which houses a priming valve that directs fluid flow, aninlet and corresponding inlet channel from the reservoir and an inletand corresponding inlet channel from an external fluid source which bothlead into the central chamber, an outflow channel leading from thecentral chamber to an outlet which is directed to the pump head, aflexible membrane covering the central chamber, a flow-through channelhaving an inlet which leads from the pump head and a fluid couplingoutlet means for fluidly connecting the catheter to the bulkhead, and aflow-through channel having a fluid coupling inlet means for fluidlyconnecting the catheter to the bulkhead and an outlet which leads to thepump section and then to the external heat exchanger. The pump sectionhas a quasi-cardioid shaped cavity, into which is positioned a rotor isfitted with a vane for moving fluid from an inlet and inlet channel toan outlet channel and outlet, a wheel assembly to facilitate movement ofthe rotor and a flow-through channel having an inlet that leads from thefeedblock section and an outlet which leads to the external heatexchanger.

In yet another aspect of the invention, the bulkhead has two components:a reservoir section and a pump section, where the pump and reservoirsections are configured similar to that described above, except that theoutlet of the reservoir section leads to the pump section and thereservoir further comprises a pressure damper and an inlet in fluidcommunication with an external fluid source.

Still another aspect of the invention relates to a cassette forsupplying heat exchange fluid to a heat exchange catheter, where thecassette comprises: (a) an external heat exchanger comprising astructural member and a compliant member, where the compliant member issealed to the structural member in a pattern that forms a flow channelbetween the compliant member and the structural member, and where theflow channel has an inlet and an outlet; (b) a first fluid supply linein fluid communication with the flow channel inlet; (c) a bulkheadcomprising a reservoir and a disposable pump head, where the reservoircontains an inlet in fluid communication with the flow channel outlet,and further has a fluid level detector for detecting the level of fluidwithin the reservoir, wherein the pump head is a cardioid vane pump headhaving an inlet and an outlet, and the pump head is actuated by anelectric motor, where the pump inlet is in fluid communication with thereservoir outlet and the electric motor is controlled by an amplifiercontroller, where the amplifier controller supplies a constant currentto the pump head thereby causing the pump head to supply a relativelyconstant pressure to the fluid in the second fluid supply line; (d) asecond fluid supply line in fluid communication with the pump outlet forreceiving fluid pumped out of the pump outlet; (e) an external fluidsource in fluid communication with the reservoir; and (f) a pressuredamper in fluid communication with the pump outlet.

Another aspect of the invention pertains to a method for providing atemperature regulated source of heat exchange fluid for heat exchangecatheters, comprising the steps of: providing a circuit comprising anexternal heat exchanger, a pump, a heat exchange catheter, and airvents, where the external heat exchanger, pump and heat exchangecatheter are in fluid communication such that fluid pumped by the pumpis circulated through the heat exchange catheter and the external heatexchanger, and the air vents allow passage of gas in and out of thecircuit through the vents but do not allow passage of liquid in and outof the circuit though the air vents; providing a heat generating orremoving unit in heat exchange relationship with the external heatexchanger; providing an external fluid source in fluid communicationwith the circuit; circulating heat exchange fluid from the externalsource through the circuit by means of pumping with the pump whilesimultaneously venting any gas contained in the circuit out through theair vents; and controlling the temperature of the heat exchanger fluidin the circuit by controlling the temperature of the heat generating orremoving unit.

BRIEF DESCRIPTION OF THE DRAWING

FIG. 1 is an illustration of the disposable fluid supply cassette of theinvention attached to a heat exchange catheter, external fluid sourceand positioned for insertion into a suitable reusable master controlunit.

FIG. 2 is an illustration of the disposable fluid supply cassette and areusable master control unit.

FIGS. 3 and 4 are exploded views of different embodiments of thedisposable fluid supply cassette of the invention.

FIG. 4A is a perspective bottom view of a fitment of the invention.

FIG. 4B is a perspective top view of a fitment of the invention.

FIG. 4C is a cross-section of the external heat exchanger taken alongline 4C—4C of FIG. 4 with no pressurized fluid therein.

FIG. 4D is a cross-section of the external heat exchanger taken alongline 4C—4C of FIG. 4 with pressurized fluid therein.

FIG. 5 is a top plan view of the bulkhead of the disposable fluid supplycassette of FIG. 3.

FIG. 5A illustrates the fluid flow pathway.

FIG. 5B is a cross-sectional view of the reservoir section taken alongline 5B—5B of FIG. 5.

FIG. 6 is a top plan view of the bulkhead of the disposable fluid supplycassette of FIG. 4.

FIG. 6A illustrates the fluid flow pathway.

FIG. 7 is an exploded view of the reservoir section of the bulkhead ofFIG. 3.

FIG. 8 is an exploded view of the feedblock section of the bulkhead ofFIG. 3.

FIG. 9 is an exploded view of the pump section of the bulkhead of FIG.3.

FIG. 10 is an exploded view of the reservoir section of the bulkhead ofFIG. 4.

FIG. 11A is a cross-sectional view of a priming valve of the inventionshown with the valve stem relaxed and the valve in the normal operatingposition.

FIG. 11B is a cross-sectional view of a priming valve of the inventionshown with the valve stem depressed and the valve in the auto-prepposition.

FIG. 12A is a top plan view of the pump section of the invention.

FIG. 12B illustrates the geometry of the pump section.

FIG. 13 is a side cutaway view of the pump head of the invention takenalong line 13—13 of FIG. 12A.

FIG. 14 is a top cut-away view of the pump wheels in place within thereusable master control unit.

FIG. 15 is a side view of the pump wheels in place within the reusablemaster control unit.

FIG. 16 is a top view of a pressure regulator valve of the invention.

FIG. 17 is a cross-sectional view of the throttle chamber taken alongline 17—17 of FIG. 16.

FIG. 18 is a cross-sectional view of a pressure damper.

FIGS. 19A, 19B and 19C are schematic illustrations of the fluid flowusing different embodiments of the disposable fluid supply cassette ofthe invention.

FIGS. 20A, 20B and 20C are side views of various embodiments of the pumpvane.

DETAILED DESCRIPTION OF THE INVENTION

The invention relates to a heat exchange fluid supply system forsupplying a heat exchange fluid to an intravascular heat exchangecatheter, which includes a disposable cassette having a pump head and anexternal heat exchanger. The system is configured to operate incombination with a reusable master control unit and an external fluidsource. The heat exchange fluid supply system of the invention isdesigned to provide an adequate supply of heat exchange fluid to thecatheter at sufficient flow rate and to provide a convenient andefficient heat exchange means to adjust the temperature of the heatexchange fluid. This system is easy to handle, inexpensive anddisposable, thus eliminating the need for extensive and time consumingsterilization between treatment of different patients. An additionalfeature of the cassette is that, due to its closed loop fluid path,sterility is maintained for the duration of operation of the catheter.

FIG. 1 illustrates the heat exchange fluid supply system of theinvention which includes disposable components including a heat exchangecatheter 160; a disposable heat exchange fluid supply cassette 5, whichincludes a pump head 139 and fluid housing 19; sensors 77, 78; and adual channel flow line 169; as well as reusable components including aheat generating or removing unit 11, a pump drive mechanism 12 andvarious controls for the unit.

The heat exchange catheter 160 is formed with a catheter flow line 162and a heat exchanger 163 which may be for example a heat exchangeballoon operated using closed-loop flow of heat exchange medium. Thecatheter shaft may be formed with a working lumen 156 for injection ofdrugs, fluoroscopic dye, or the like, and for receipt of a guide wire157 for use in placing the heat transfer catheter at an appropriatelocation in the patient's body. The proximal end of the shaft may beconnected to a multi-arm adapter 151 for providing separate access tovarious channels in the catheter shaft. For example, one arm 152 mayprovide access to the working lumen 156 of the catheter shaft forinsertion of a guide wire 157 to steer the heat transfer catheter to thedesired location. Where the internal heat exchanger 163 is a heatexchange balloon for closed-loop flow of a biocompatible fluid thatserves as the heat exchange medium 35, the adapter 151 may contain anarm 153 to connect an inlet flow line 150 to an inlet flow channel (notshown) within the catheter shaft, a separate arm 154 to connect anoutlet fluid line 158 to an outlet flow channel (also not shown). Thedual channel flow line 169 may contain both the inlet and outlet flowlines 150, 158 to connect the catheter flow line 162 to the disposableheat exchange fluid supply cassette 5. Additionally, one of the flowlines, for example the inlet flow line 150 may be connected to anexternal fluid source 15 of heat exchange medium 35 to prime theclosed-loop heat exchange balloon catheter system as necessary. Theexternal fluid source 15 may also be directly connected to the cassette5, as is shown in other embodiments of the invention.

The heat exchange cassette 5 may include fluid housing 19 configured ina serpentine pathway for the heat exchange fluid to be pumped throughthe cassette by means of a disposable pump head 139. The heat exchangecassette, including the serpentine pathway and the pump head 139 isconfigured to install into a reusable master control unit 185. Themaster control unit may include a heat generating or removing unit 11such as a solid state thermoelectric heater/cooler (TE cooler). A TEcooler is particularly advantageous because the same unit is capable ofeither generating heat or removing heat by changing the polarity ofcurrent activating the unit. Therefore it may be conveniently controlledto supply or remove heat from the system without the need of twoseparate units.

The master control unit includes a pump drive mechanism 12 thatactivates the pump head 139 to pump the heat exchange fluid 35 and causeit to circulate through the catheter's heat exchanger 163 and theserpentine path of the fluid housing 19 in the heat exchange cassette.When installed, the fluid housing 19 is in thermal communication withthe TE cooler, and thus the TE cooler may act to heat or cool the heatexchange fluid as that fluid is circulated through the serpentinepathway. When the heat exchange fluid is circulated through the internalheat exchanger 163 located in a patient's body, it may act to add orremove heat from the body. In this way the TE cooler may act to affectthe blood temperature of a patient as desired.

The TE cooler and the pump head are responsive to a control unit 13. Thecontrol unit receives data input through electrical connections 63, 64,65 to numerous sensors, for example body temperature sensors 77, 78 thatmay sense temperatures from a patient's ear, brain region, bladder,rectum, esophagus or other appropriate location as desired by theoperator who places the sensors. Likewise, a sensor 82 may monitor thetemperature of the heat exchange balloon, and other sensors (not shown)may be provided as desired to monitor the blood temperature at thedistal tip of the catheter, at the proximal tip of the balloon, or otherdesired location.

An operator by means of the manual input unit 14 may provide theoperating parameters of the control system, for example a pre-selectedtemperature for the brain. These parameters are communicated to thecontrol unit 13 by means of a connection between the manual input unitand the control unit In practice, the operator using the manual inputunit supplies a set of parameters to the control unit. For example, adesired temperature for the brain region and/or the whole body of thepatient may be specified as the preselected temperature. Data isreceived from the sensors 77, 78 indicating for example, a sensedtemperature of the patient at the location of the sensors, e.g. theactual core body temperature of the patient or the actual temperature ofthe brain region. Other data input may include the actual temperature ofthe heat exchanger, the temperature of blood at the distal end of thecatheter body, or the like.

The control unit 13 coordinates the data and selectively actuates thevarious units of the system to achieve and maintain parameters. Forexample, it may actuate the TE cooler 11 to increase the amount of heatit is removing if the actual temperature is above the specifiedtemperature, or decreasing the amount of heat being removed if thetemperature is below the specified temperature. It may stop the pumpingof the heat exchange fluid when the body or regional temperature sensedis the desired temperature, or it may stop pumping in response to otherpre-determined criteria.

The control unit 13 may have a buffer range for operation wherein atarget temperature is established, and an upper variance set pointtemperature and lower variance set point temperature are also set. Inthis way, the control unit may cause the heat exchanger to operate untilthe target temperature is reached. At that temperature, the control unitmay suspend the operation of the heat exchanger until either the uppervariance set point temperature is sensed or the lower variance set pointtemperature is reached. When the upper variance set point temperature issensed, the control unit would then activate the heat exchanger toremove heat from the blood stream. On the other hand, if the lowervariance set point temperature is sensed, then the control unit wouldactivate the heat exchanger to add heat to the blood stream. Such acontrol scheme as applied to this system has the advantage of allowingthe operator to essentially dial in a desired temperature and the systemwill act to reach that target temperature and maintain the patient atthat target temperature. At the same time, a buffer range is establishedso that when the target temperature is reached, the control unit 13 willgenerally not turn the TE cooler 11 on and off or activate anddeactivate the pump drive mechanism 12 in rapid succession, actions thatwould be potentially damaging to the electric units in question.

It may also be perceived, in keeping with the present invention, thatthe control unit 13 may be configured to simultaneously respond toseveral sensors, or to activate or deactivate various components such asseveral heat exchangers. In this way, for example, a control unit mightheat blood that is subsequently circulated to the core body in responseto a sensed core body temperature that is below the target temperature,and simultaneously activate a second heat exchanger to cool blood thatis directed to the brain region in response to a sensed braintemperature that is above the target temperature. It may be that thesensed body temperature is at the target temperature and thus the heatexchanger that is in contact with blood circulating to the core body maybe turned off by the control unit, while at the same time the controlunit continues to activate the heat exchanger to cool blood that isdirected to the brain region. Any of the many control schemes that maybe anticipated by an operator and programmed into the control unit arecontemplated by this invention.

An advantage of the system as illustrated is that all the portions ofthe system that are in contact with the patient are disposable, butsubstantial and relatively expensive portions of the system arereusable. Thus the catheter, the flow path for sterile heat exchangefluid, the sterile heat exchange fluid itself, and the pump head are alldisposable. Even if a rupture in the heat exchange balloon permits theheat exchange fluid channels and thus the pump head to come in contactwith a patient's blood, no cross-contamination will occur betweenpatients because all those elements are disposable. The pump drivemechanism, the electronic control mechanisms, the TE cooler, and themanual input unit, however, are all reusable for economy andconvenience. Likewise, the sensors may be disposable, but the controlunit to which they attach is reusable.

The system of FIG. 1 can also be readily modified within the scope ofthe instant invention. For example, but not by way of limitation, theserpentine pathway may be a coil or other suitable configuration, thesensors may sense a wide variety of body locations and other parametersmay be provided to the control unit, such as temperature or pressure,the heat exchanger may be any appropriate type, such as a thermalelectric heating unit which would not require the circulation of heatexchange fluid. If a heat exchange balloon is provided, a pump headmight be provided that is a screw pump, a gear pump, diaphragm pump, aperistaltic roller pump, or any other suitable means for pumping theheat exchange fluid. All of these and other substitutions obvious tothose of skill in the art are contemplated by this invention.

In one embodiment of the invention, a disposable cassette for supplyinga heat exchange fluid to a heat exchange catheter, comprises: anexternal heat exchanger comprising a structural member and a compliantmember, where the compliant member is sealed to the structural member ina pattern, and the pattern forms one or more flow channels between thecompliant member and the structural member, the flow channel having aninlet and an outlet; a first fluid supply line, the first fluid supplyline being in fluid communication with the flow channel inlet; a pumphead contained in the disposable fluid supply cassette, and having apump inlet and a pump outlet, where the pump inlet is in fluidcommunication with the external heat exchanger flow channel outlet forpumping fluid from the flow channel outlet; a second fluid supply line,the second fluid supply line being in fluid communication with the pumpoutlet for receiving fluid pumped out of the pump outlet; and a pressureregulator, the pressure regulator being in fluid communication with thepump outlet for regulating the pressure of fluid pumped from the pumphead.

Referring to FIGS. 1-4, an exemplary disposable cassette 5 for supplyinga heat exchange fluid 35 to a heat exchange catheter 160 is shown. Thecassette 5 comprises an external heat exchanger 20. The external heatexchanger can any be a combination of one or more structural andcompliant members such that the overall configuration of the externalheat exchanger is adapted to mate with the heat generating or removingunit. In a preferred embodiment, the structural member is a back plate26 and the compliant member is heat exchange layer 28. The heat exchangelayer is sealed to the back plate in a pattern which forms a flowchannel 34 between the back plate and the heat exchange layer, and theflow channel has an inlet 36 and an outlet 38.

The cassette 5 also includes a first fluid supply line that is in fluidcommunication with the flow channel inlet 36. The pump head 139 has apump inlet 113 and a pump outlet 115, where the inlet in fluidcommunication with the external heat exchanger flow channel outlet 38and serves to pump fluid from the flow channel outlet. A second fluidsupply line is in fluid communication with the pump outlet 115 andreceives fluid that is pumped out of the outlet. The cassette 5 alsoincludes a pressure regulator that is in fluid communication with thepump outlet. The disposable cassette is configured such that when thefirst and second fluid supply lines are connected to a heat exchangecatheter, a fluid circuit is created and includes the external heatexchanger, pump head, the fluid lines and the catheter.

In another embodiment of the invention, a heat exchange fluid supplysystem for a heat exchange catheter comprises: an external heatexchanger comprising a structural member and a compliant member, wherethe compliant member is sealed to the structural member in a pattern,the pattern forming a flow channel between the compliant member and thestructural member, and the flow channel having an inlet and an outlet; afirst fluid supply line, the first fluid supply line being in fluidcommunication with the flow channel inlet; a bulkhead, the bullheadcomprising a pump head and a reservoir, the reservoir having a reservoirinlet and a reservoir outlet, the reservoir inlet being in fluidcommunication with the external heat exchanger flow channel outlet, thepump head having a pump inlet and a pump outlet, the pump inlet being influid communication with the reservoir outlet for pumping fluid from thereservoir outlet; a second fluid supply line, the second fluid supplyline being in fluid communication with the pump outlet for receivingfluid pumped out of the pump outlet; and an external fluid source, theexternal fluid source being in fluid communication with the bulkhead.Referring more particularly to the cassette shown in FIGS. 3 and 4, andthe overall system of FIG. 2, this system comprises the external heatexchanger 20 and fluid supply lines as described above. In addition, thecassette comprises a bulkhead (30, 330) that comprises a pump head 140and a reservoir (58, 358). The reservoir has a reservoir inlet that isin fluid communication with the external heat exchanger flow channeloutlet 38 and a reservoir outlet (62, 362). The pump head has a pumpinlet 113 and a pump outlet 115, and the pump inlet is in fluidcommunication with the reservoir outlet (62, 362) for pumping fluid fromthe reservoir outlet. The heat exchange fluid supply system also caninclude an external fluid source 15 that is in fluid communication withthe bulkhead.

One embodiment of the invention is a heat exchange fluid supply systemfor supplying a heat exchange fluid to an intravascular heat exchangecatheter, which includes a disposable cassette having a bulkhead and anexternal heat exchanger. The bulkhead includes a reservoir section and apump section which are in fluid communication with each other. Thereservoir section is provided with a means to monitor the amount of heatexchange fluid that is in the system. The system may optionally comprisea mechanism for priming the system with heat exchange fluid from anexternal source and for circulating fluid to the catheter in a closedcircuit, which is preferably a valve having a first position whereby thesystem is primed with heat exchange fluid from an external source and asecond position where the fluid is circulated to the catheter in aclosed circuit. In the absence of this valved-priming system, the systemis passively primed. The pump section is configured to allow for pumpingof heat exchange fluid at a constant pressure. This aspect of theinvention is illustrates in FIG. 2, which shows one embodiment of thedisposable heat exchange fluid supply cassette 10 having a bulkhead 30and an external heat exchanger having an inlet and an outlet, depictedin FIG. 2 as external heat exchanger 20. The cassette is configured tooperate in combination with a reusable master control unit 186, whichwill typically be provided with a power supply and a heat generating orremoving unit, and other parts that cooperate with the cassette 10, thedetails of which will be described in detail below.

One embodiment of the cassette of the invention is shown in FIG. 3 andincludes a disposable fluid supply cassette 10 has an external heatexchanger 20 coupled to a bulkhead 30 by means of a cover plate 168. Thebulkhead includes a reservoir section 40, an optional feedblock section80 and a pump section 100, the details of which are described below. Thesections can be independent and discrete units that are coupledtogether, as shown in FIG. 2. The invention also contemplates housingmore than one section together in a single unit This may be desired forease in manufacturing and assembly. The sections can be machined, moldedor cast and are typically of a durable material such as plastic orPlexiglas.

The feedblock is configured to communicate with an external fluid source15, which can be any suitable source of biocompatible fluid, by means ofan external fluid providing line 16. The fluid line 16 may be providedwith a pinch clamp 21. The source of biocompatible fluid can be forexample, an IV bag of saline. Bag size is not critical but has a typicalcapacity of about 250 ml. In addition, the feedblock communicates withan intravascular heat exchange catheter 160, by means of fluid supplyline 150 and fluid return line 158. The external fluid providing, fluidsupply and fluid return lines are typically of a flexible compressiblematerial such as polyvinylchloride or other suitable flexiblecompressible tubing material. The disposable fluid supply cassette 10can be packaged with or separately from the heat exchange catheter 160.

Another embodiment of the disposable heat exchange fluid supply cassetteof the invention is shown in FIG. 4. The disposable fluid supplycassette 310 has an external heat exchanger 20 coupled to a bulkhead 330by means of a cover plate 368. The bulkhead includes a reservoir section340 and a pump section 300. The reservoir section 340 is configured tocommunicate with the external fluid source by means of an external fluidproviding line. In addition, the pump section 300 communicates with theintravascular heat exchange catheter by means of a fluid supply line anda fluid return line.

The cassette of the invention is initially primed, that is, filled withheat exchange fluid from an external source and excess air removed. Thispriming of the system of the invention can be accomplished in numerousways. One embodiment of the invention utilizes a “valved-priming”mechanism, and is illustrated by the embodiment of FIG. 3. Thisvalved-priming mechanism involves a priming sequence having a valve orthe like controlling temporary fluid input from an external fluidsource, and once the system is primed, the valve prevents further fluidinput from the external source and the fluid flow becomes a closedcircuit within the cassette 10 and the catheter 160. In the embodimentof FIG. 3, the valved-priming mechanism is contained within a discreteunit referred to as the feedblock section. It is understood however,that the valved-priming mechanism can be located in another portion ofthe bulkhead, for example as part of the pump or reservoir section, andstill serve the same function. During priming, heat exchange fluid fromexternal fluid source 15 flows through the external fluid providing line16 and enters the feedblock section 80, and then flows into the pumpsection 100. From the pump section, the fluid is pumped out throughfluid supply line 150, which is coupled to the catheter inlet of theheat exchange catheter 160. It is thereafter circulated through thecatheter, back through the fluid return line 158 to the external heatexchanger 20, through the external heat exchanger and into thereservoir. As the fluid is pumped into the reservoir, air displaced bythe fluid escapes through the hydrophobic vents 54. This generallycontinues until the system is full of heat exchange fluid and excess airhas been vented out of the system. At this point in the process, thevalve is closed from the external fluid source and the fluid supplycircuit between the catheter and the cassette is a closed circuit. Thispriming occurs prior to the insertion of the heat exchange catheter intothe patient, with the heat exchange balloon outside the body. Thevalved-priming is described in greater detail below in connection withFIGS. 5, 8, 11A and 11B.

Another embodiment of the invention utilizes a “passive-priming”mechanism and is illustrated by the embodiment of FIG. 1 and FIG. 4.This passive-priming mechanism involves fluid input from the externalfluid source 15, which serves to fill the system. The external fluidsource 15 is generally hung or placed at a location above the reservoir,and is connected by means of an external fluid providing line 16directly or indirectly to the reservoir in the cassette 310. Fluid movesinto the reservoir, the pump is activated, and as described above inconjunction with the valved-priming, the fluid is pumped through thesystem and excess air is expelled out through the hydrophobic vents 54.Once the system is primed, the amount of fluid needed to maintain thesystem in a full condition may change slightly due primarily to changesin the compliance of the system at different temperatures. Toaccommodate this, additional fluid may enter the system from theexternal fluid source to maintain the filled condition, and similarly,excess fluid may leave the system and reenter the external fluid source.This has the advantage of maintaining a relatively uniform fluid levelby automatic action. As with the valved-priming, this is generally donebefore the catheter is inserted, with the balloon outside the patient'svascular system.

As indicated above, the disposable cassette comprises an external heatexchanger, which is formed of a combination of one or more structuraland compliant members. In a preferred embodiment, the structural memberis a stiff back plate 26 and the compliant member is a flexible heatexchange layer 28, which are fused together to form a serpentine flowchannel or a plurality of flow channels, and having an inlet orifice andan outlet orifice that communicate with the bulkhead. The external heatexchanger is positioned so as to be in a heat transfer relationship witha heat generating or removing unit provided in the reusable mastercontrol unit, as shown in FIGS. 1 and 2. There are numerous heatexchangers that can be used with the disposable cassette of theinvention. Due to the configuration of the external heat exchanger, theheat generating or removing unit is preferably a flat thermallyconducting plate which is heated or cooled to add or remove heat fromthe heat exchange fluid.

Turning to FIG. 4, the external heat exchanger 20 is shown as having twolayers, a relatively stiff back plate 26 that functions as a structuralmember and a thinner heat exchange layer 28 that functions as thecompliant member. The back plate 26 is typically made of a high densitypolyethylene and is generally about 0.030 inches (30 mils) thick. Thethinner heat exchange layer is shown in this embodiment as being sealedin a serpentine pattern to the back plate by fusing such as by heatsealing or other suitable technique to permanently adhere the two layerstogether. The pattern of heat sealing creates a serpentine pathwaycomposed of sealed portions 32 separating a serpentine flow channel 34or a plurality of flow channels. The sealed portions 32 provide for thechannels 34 to be continuous. The winding flow channels 34 form apathway which causes the heat exchange fluid to flow back and forthadjacent to and in heat transfer relationship with the heat generatingor removing unit, and ensures that the fluid circulates proximate to theheat generating or removing unit for a sufficient amount of time toallow for adequate heating or cooling of the fluid. The invention alsoencompasses utilizing sealed portions that are not continuous, as longas the sealed portions are configured so as to create channels thatpermit fluid flow through the external heat exchanger 20. In addition,the external heat exchanger can be configured to have a V-shaped leadingedge 23 that acts as a guide to facilitate placement into the controlunit 186.

The thinner heat exchange layer is generally about 4 to 8 mils, and istypically a low density polyethylene material, and is slightlyelastomeric or compliant so that when pressurized heat exchange fluid 35is placed into the legs of the channels, they bow out slightly as may beseen in FIGS. 4C (uninflated) and 4D (inflated). Since the back plate 26and thinner heat exchange layer 28 are both polyethylene, they weldtogether effectively by means of heat welding. However, the bulkhead 330is not the same material, and therefore the external heat exchanger issealed to the bulkhead by other means, such as by a mechanical pressureseal.

The external heat exchanger 20 is provided with an extended attachment48 whereby the external heat exchanger may be sealed to the bulkhead330. The extended attachment 48 has three sections, a first flap section142, a cutaway section 144 and a second flap section 146. One or morevent holes 52 are cut into the first flap section 142 to allow air tovent from the corresponding number of hydrophobic gas permeable vents 54over a fluid reservoir, as will be described in greater detail below.While a plurality of vent holes 52 is shown in the embodiment of FIG. 4,any suitable shape or number of holes will suffice, for example a singlevent hole is shown in the embodiment of FIG. 3.

The external heat exchanger 20 also has an inlet orifice 36 and anoutlet orifice 38, which allows the heat exchange fluid to exit thebulkhead, circulate through the external heat exchanger (positioned in aheat transfer relationship with a heat generating or removing unit) andthen enter the bulkhead after being heated or cooled. Each orifice isprovided with a fitment that allows fluid to flow into the space betweenthe thin heat exchange layer 28 and the back plate 26. When heatexchange fluid is pumped into the inlet orifice 36 through a firstfitment 22, it winds its way along the serpentine path to outlet orifice38 and then enters the bulkhead through a second fitment 24. The entireexternal heat exchanger is lain on a hot or cold plate of a heatgenerating or removing unit such as the heat exchange surface of athermoelectric cooler, with the thinner heat exchange layer 28positioned against the hot or cold plate. In this way, the temperatureof heat exchange fluid may be controlled by controlling the temperatureof the hot or cold plate and pumping fluid through the external heatexchanger.

Fitments 22, 24 are secured within the inlet and outlet orifices 36, 38.The fitments are constructed as illustrated in FIGS. 4A and 4B forfitment 24. Each fitment has a bored channel, a base plate 44, and aplurality of spacer protrusions 46 on the lower surface of the baseplate. The embodiment of FIG. 4B illustrates four such protrusions butthe invention contemplates having fewer or more than four protrusions.When the fitments are placed in the external heat exchanger, the channelexits the orifice, and the base plate is tightly positioned between theheat exchange layer 28 and the back plate 26. The spacer protrusionsspace the base plate away from the back plate of the external heatexchanger so that fluid contained within channels 34 passes between theprotrusions, through fitment channel 37, and then into bulkhead 330.Similarly, fluid returning from the heat exchange catheter enterschannels 34 through a bored channel in fitment 22, passes between theprotrusions and flows into the channels. Two O-rings, such as flexiblerubber washers, can be positioned around the periphery of the topsection 148 of each fitment and are positioned between the heat exchangelayer 28 and the bulkhead 30. The reservoir section has an inlet hole56, while the pump section has an outlet hole 57. The fitment topsection 148 of fitment 24 is sized to be inserted into inlet hole 56 andthe corresponding top section of fitment 22 is sized to be inserted intooutlet hole 57.

FIGS. 7, 8 and 9 are exploded views of the bulkhead 30 of the embodimentof FIG. 3 and its components, while FIGS. 5 and 5A illustrate theassembled bulkhead 30. Similarly, FIG. 10 is an exploded view of one ofthe reservoir section 340 component of the bulkhead 330 of theembodiment of FIG. 4, while FIGS. 6 and 6A illustrate the assembledbulkhead 330.

Referring to FIGS. 7, 5 and 5A, the reservoir section 40 has an inlethole 56 leading from the external heat exchanger 20 and an outletchannel 62 leading to the feedblock section 80, a fluid reservoir 58with an indented area 60 for storage of heat exchange fluid, a fluidlevel detector 69 for monitoring the level of heat exchange fluid withinthe fluid reservoir, an optional mounting block 75 for positioning of anoptional pressure regulator valve useful for controlling the pressurefor heat exchange fluid flow from the feedblock section to the catheter,a reservoir cover plate 53 that serves to retain fluid within thereservoir. The cover plate 53 seals the reservoir but is fitted with oneor more vent holes 55 into which are positioned a corresponding numberof hydrophobic gas permeable vents 54 for releasing air contained withinthe fluid reservoir. The reservoir section 40 of FIG. 5 also is shownwith a mounting block 75 for the pressure regulator valve 76. Thefunction of the pressure regulator will be described in greater detailbelow. The fluid reservoir 58 can also be configured so as to have anindented area 60 in the base, optionally covered with a partial lid 61.The lid 61 provides a fluid tight cover over the indented area exceptfor a slit 59 which is open between the indented area 60 and theinterior of the reservoir in an area near the prisms 69, 74. In this waythe fluid opening leading to the reservoir outlet channel is locatednear the prisms and the prisms will most accurately reflect the fluidlevel available to the feedblock and thus the pump. This is seen in theembodiment of FIG. 5B. Heat exchange fluid enters the fluid reservoir 58from the inlet hole 56, collects in the reservoir and then flows intothe reservoir outlet channel 62. The reservoir outlet is at the base ofthe fluid reservoir 58 and is fluidly connected to an inlet 87 andinflow channel 86 of the feedblock section. This may be accomplished bythe snug fitting of an outlet collar 66 at the outlet channel 62 fromthe reservoir over a cylindrical protrusion 68 of the feedblock sectioninlet.

Referring to FIGS. 8, 5 and 5A, the feedblock section 80 has a centralchamber 90 which houses a priming valve 84 that directs fluid flow, aninlet 87 and corresponding inlet channel 86 from the reservoir and afill port 18 and filling channel 88 from an external fluid source whichboth lead into the central chamber, an outflow channel leading 92 fromthe central chamber to an outlet 93 which is directed to the pump, aflexible membrane 96 covering the central chamber, an optional pressureregulator chamber 198 adjacent to an optional sensing chamber 224(having a diaphragm 204 and push rod 210) which communicates with thepressure regulator valve when present, an optional pressure damper (notshown), an outlet channel 219 leading from the sensing chamber or damperto a fluid coupling outlet means 149 in the feedblock section forfluidly connecting the bulkhead to the catheter fluid supply line 150,an inlet 95 and channel 196 which connects the pump to the sensingchamber or damper, and a flow-through channel 221 having a fluidcoupling inlet means 159 for fluidly connecting the catheter fluidreturn line 158 to the bulkhead and an outlet 97 which leads to the pumpsection and then to the external heat exchanger. The priming valve 84can be any suitable mechanism and is illustrated in the embodiment ofFIGS. 8, 5 and 5A as a spool valve.

Referring to FIGS. 10, 6 and 6A, the reservoir section 340 has an inlethole 56 leading from the external heat exchanger 20 and an outletchannel 362 leading to the pump section 300, a fluid reservoir 358 forstorage of heat exchange fluid, a fluid level detector 369 formonitoring the level of heat exchange fluid within the fluid reservoir,a reservoir cover plate 353 that serves to retain fluid within thereservoir. The cover plate 353 seals the reservoir but is fitted with aone or more vent holes 55 into which are positioned a correspondingnumber of hydrophobic gas permeable vents 354 for releasing aircontained within the fluid reservoir. The reservoir section 340 also hasa fill port 318 connected to an external fluid source, and a pressuredamper, which comprises a pressure dampening chamber 230 filled with acompressible material 232. The reservoir section is fitted with a collar371 that couples the dampening chamber to the pump section.

The pressure of fluid flowing from the bulkhead to the catheter throughfluid supply line 150, can be controlled in numerous ways. In theembodiment of FIG. 3 the pressure is controlled by a pressure regulatorvalve. However, a pressure regulator valve and the chambers that operatewith it are optional features and may be replaced by a constant currentsystem and a pressure damper, which is illustrated in FIG. 18.

In the embodiment of the invention having a pressure regulator valve,the fluid supply system is configured to have a reservoir section, afeedblock section and a pump section, where the pressure regulator iscontained within the feedblock section. It is understood however, thatthe pressure regulator can be located in another portion of thebulkhead, for example as part of the pump or reservoir section, andstill serve the same function. The pressure regulator comprises thepressure regulator valve that controls the pressure of the fluid flowfrom the feedblock section to the catheter mounted in the reservoirsection. The pressure regulator also comprises a pressure regulatorchamber (having a counter spring and counter spring block) adjacent to asensing chamber (having a diaphragm and push rod) which communicateswith the pressure regulator valve. Both the pressure regulator chamberand the sensing chamber are housed in the feedblock section. Thefeedblock section also has an outlet channel leading from the sensingchamber to an outlet in the feedblock section which leads to thecatheter and an inlet and inlet channel which connects the pump to thesensing chamber. One embodiment of the pressure regulator is shown inthe embodiments of FIGS. 5 and 5A, where the reservoir section 40,feedblock section 80 and pump section 100 are shown as being coupledtogether, and the pressure regulator comprises the pressure regulatorvalve 76, a pressure regulator chamber 198 (with counter spring 222 andcounter spring block 220) adjacent to a sensing chamber 224 (with adiaphragm 204 and push rod 210) which communicates with the pressureregulator valve. An outlet channel 219 on the feedblock section leadsfrom the sensing chamber to a fluid coupling outlet means 149 in thefeedblock section and serves to fluidly connect the bulkhead to catheterfluid supply line 150, while an inlet 95 and inlet channel 196 connectsthe pump to the sensing chamber.

The pump head can be any type such as is well known in the art, forexample, a vane pump, a diaphragm pump, a peristaltic pump, an impellerpump, a gear pump and so forth. A preferred embodiment utilizes acardioid vane pump, as shown in FIGS. 5 and 9. The pump section 100 hasa quasi-cardioid shaped cavity 104, into which is positioned a pump head140 that comprises a rotor 106, a vane 110 for moving fluid from aninlet 113 and inlet channel 112 to an outlet channel 114 and outlet 115,a wheel assembly for coupling to the motor and to facilitate movement ofthe pump head, for example a plurality of wheels 134, 136, and 138, anda flow-through channel 143 having an inlet 141 that leads from thefeedblock section 80 and an outlet hole 57 which leads to the externalheat exchanger 20. Referring to the embodiment shown in FIG. 6, the pumpsection 300 has the same shaped cavity 104 and pump head parts asdescribed for the embodiment of FIG. 5. The vane 110 moves fluid frominlet 113 and inlet channel 112 to the pump outlet channel 314. The pumpsection 300 also has a flow-through channel 343 having a fluid couplinginlet means 159 that leads from the catheter and an outlet hole 57 whichleads to the external heat exchanger 20. The pump outlet channel 314 isindependently in fluid communication with a pressure dampening chamber230. Outlet channel 314 is also configured with a fluid coupling outletmeans 149 for fluidly connecting the bulkhead to the catheter. Fluidmoving along this pathway encounters an opening 250 that exposes thefluid to the compressible material 232 within the dampening chamber. Thepump is able to pump fluid through the system at pressure in excess of35 psi. More critical to the invention, the pump is able to rapidlyachieve and maintain a predetermined pressure, for example 40 psi.

In the embodiment of FIGS. 3 and 7-9, the reservoir section 40 is shownas being coupled to the feedblock section 80 which in turn is shown asbeing coupled to the pump section 100; however, at least two of thesesections can be housed together in one unit These sections can bereadily coupled as follows. The reservoir section 40 has two collars:outlet collar 66 and pressure regulator collar 67. These fit tightlyover two collars of slightly smaller size positioned on the feedblocksection, the inlet collar 85 and sensing chamber collar 225. Thefeedblock section has three additional collars: outlet collar 81, inletcollar 83 and outlet collar 89, around which are positioned O-rings 228.Collar 81 fits snugly with inlet 141, collar 83 fits snugly with outlet115 and collar 89 fits snugly with inlet 113. In the embodiment of FIGS.4 and 10, the reservoir section 340 is readily coupled to the pumpsection 300 by means of a collar 371 on the reservoir section that fitsinto a matching sleeve on the pump section 300, and an outlet channel362 that fits in the bottom of an L-shaped channel on the pump section.Any of the aforementioned sections in FIGS. 3 and 4 may further besecured with appropriate adhesive if desired.

The reservoir section can be provided with a means to monitor the amountof heat exchange fluid that is in the system, more specifically anoptical means for detecting the level of fluid contained within thefluid reservoir. Since the heat exchange fluid is a biocompatible fluidand the volume of the external source is about 250 ml, it is notexpected that fluid leakage into the patient will be problematic.However, the heat exchange fluid supply system of the invention isdesigned to detect the level of the fluid in the system so that awarning or other measure can be instituted if the system becomesunacceptably low.

Accordingly, in one aspect of the invention, the reservoir section isprovided with a means to detect the fluid level in the reservoir andcomprises at least one prism mounted within the reservoir sectionadjacent the inside of a relatively transparent window or wall portionin the reservoir, and at least one optical beam source and at least oneoptical beam sensor mounted on the reusable master control unit adjacentthe outside of the window.

In one embodiment, the fluid level detector comprises a prism mounted inthe reservoir, a light beam source and a light beam sensor. The prismhas a diffraction surface and the light beam source directs a light beamagainst that surface. The prism is configured so that when thediffraction surface is in contact with air, the light beam is reflectedto impinge on the light beam sensor and the sensor generates a signal.Likewise, when the diffraction surface is in contact with fluid, thelight beam does not reflect to the sensor and the sensor does notgenerate a signal.

In operation, a light beam is directed through the reservoir section andagainst the prism at a particular point along its angled length. Thesensor is located to detect the presence or absence of a reflected beam.As long as the fluid reservoir remains full and the fluid level is at apre-determined elevation above the point of impingement of the lightbeam, the diffraction surface of the prism at that point is in contactwith the fluid. Therefore, the light beam directed at the prism travelsthrough the prism and, upon reaching the diffraction surface, isreflected such that the sensor does not observe a reflected beam. If thefluid falls below the pre-determined elevation, the diffraction surfaceof the prism at the point where the beam impinges on it will no longerbe in contact with the fluid and will be in contact with air instead.Air has a different index of refraction than the index of refraction ofthe fluid. Accordingly, upon reaching the diffraction surface, thereflected beam will no longer reflect out to the same point, and isreflected in such a manner that it impinges upon the sensor, which willthen observe a reflected beam.

In a preferred embodiment, two prisms, each having a corresponding beamsource and beam, are utilized. Each prism will have a corresponding beamsource and sensor mounted on the reusable master control unit at alocation adjacent to the prism. For example, FIG. 2 illustratesplacement of an optical beam source 166 and optical beam sensor 167 forthe first prism 72 in the bulkhead design of FIG. 3. An adjacent beamsource and sensor would also be provided for the second prism 74, ifpresent. For the bulkhead design of FIG. 4, the beam source(s) andsensor(s) would be position on the control unit 186 at a locationunderneath the fluid level detector 369. The second prism/source/sensoris redundant and functions to monitor the same fluid level as the firstprism but operates as a safety mechanism in the even the firstprism/source/sensor fails to function properly. Alternatively, one ofthe prisms may also have a “high level” sensing system that can be usedto signal the control unit when the fluid in the reservoir reaches acertain high level. This is useful, for example, when the valved-primingsystem is used and detection of a high or full level is needed todetermine when to activate the valve to stop the priming sequence.

Referring to FIG. 7, a relatively transparent bulkhead material or arelatively transparent window 70 configured in the bulkhead allows foroptical observation of the fluid level in the fluid reservoir 58 throughthe end of the reservoir section 40. First and second prisms 72, 74 aremounted at the end of the fluid reservoir near the inlet hole 56. In theembodiment of FIG. 9, first and second prisms 372, 374 are mountedwithin the fluid reservoir near the pressure dampening chamber 230.These prisms have a diffraction surface and may be machined separatedand then affixed within the reservoir section or they may be machined aspart of the section, and are made of a material such as polycarbonate.Although only one prism is needed for the fluid level detection methodto function, it may be desirable to include a second redundant prism asdescribed above.

If desired, both high level and low level sensors can be employed oneach prism. The sensors will generate a signal indicating that eitherthere is or is not fluid at the level of the optical beam. If theoptical beam source and sensor are positioned or the optical beam isdirected near the top of the tank, the indication that the fluid hasreached that level will trigger the appropriate response from thecontrol system, for example to terminate a fill sequence. On the otherhand, if the sensor is positioned or optical beam directed to sense thefluid level on the bottom of the tank, then the fluid level detector isconfigured to detect a low fluid level and can generates a signalrepresenting such low level. The cassette can then be configured torespond to this signal indicative of a low level of fluid in thereservoir. For example, the pump head can be designed to be responsiveto this signal such that the pump head stops pumping when a low fluidlevel is detected, so that air will not be pumped into the heat exchangecatheter.

In a preferred embodiment of the invention, the reservoir section isprovided with a means to detect when the fluid reservoir is too low. Inoperation, the optical beam source is turned on to produce an opticalbeam that is directed towards the bottom of the prism and is reflectedback to the optical beam sensor. Typically, this source would beginoperation after the reservoir had started to fill with fluid. Thus,fluid would be in the reservoir and so the sensor will not observe areflected light beam. As long as this is the case, the pump willcontinue to operate, moving fluid through the cassette and catheter.However, if the fluid level drops below the level of the optical beam,the sensor then will observe a reflected light beam, which will triggerthe pump to cease operation and the system to shut down.

In the embodiment of the invention that involves a valved-primingsequence, the optical beam source is turned on to produce an opticalbeam that is directed towards the top of the prism and is reflected backto the optical beam sensor. As long as the sensor observes a reflectedlight beam, the fill operation of the cassette continues to run. As thefluid level rises, at some point it reaches a level such that theoptical beam is deflected and no longer reflects back to the sensor.When the sensor no longer observes a reflected light beam, the filloperation of the cassette ceases.

This is illustrated by referring to FIGS. 8, 11A and 11B, where thebulkhead is shown as further comprising a chamber 90 that houses a valve84. The chamber has a first chamber inlet 18 that is in fluidcommunication with the external fluid source 15, a second chamber inlet87 in fluid communication with the reservoir outlet 62, and a chamberoutlet 93 in fluid communication with the pump inlet 113. The valve isdesigned to have a first position whereby the first chamber inlet isopen, the second chamber inlet is closed and fluid flows from theexternal fluid source to the pump inlet. In the second position of thevalve, the first chamber inlet is closed, the second chamber inlet isopen and fluid flows from the reservoir outlet to the pump inlet. Inthis embodiment, the fluid level detector is configured to detect a lowfluid level and a high fluid level, and the detector generates a firstsignal representing the low level and a second signal representing thehigh level. Initially, the valve is in its first position and ismaintained in this first position in response to the first signalthereby allowing fluid to enter reservoir until it reaches a high level,at which point the detector generates a second signal, and the valve isactuated to its second position.

FIGS. 5 and 6 also provide another view of the three hydrophobic gaspermeable vents 54 located in the top of the reservoir section 40 and340, and positioned over the fluid reservoir 58 and 358. These ventsserve to purge air from the fluid supply by allowing gas such as air toescape, but will not vent fluid. In this way, as the fluid reservoirfills up, the air in the reservoir can be vented to the atmosphere,while not permitting any heat exchange fluid to escape. In addition thepore size on the vents is small enough to prevent the entrance of anycontaminants such as microbes, thus maintaining the sterility of thefluid that is being circulated through the catheter in the patient'sbody.

One embodiment of the invention pertains to a method for providing atemperature regulated source of heat exchange fluid for heat exchangecatheters, comprising the steps of: providing a circuit comprising anexternal heat exchanger, a pump, a heat exchange catheter, and airvents, where the external heat exchanger, pump and heat exchangecatheter are in fluid communication such that fluid pumped by the pumpis circulated through the heat exchange catheter and the external heatexchanger, and the air vents allow passage of gas in and out of thecircuit through the vents but do not allow passage of liquid in and outof the circuit though the air vents; providing a heat generating orremoving unit in heat exchange relationship with the external heatexchanger, providing an external fluid source in fluid communicationwith the circuit; circulating heat exchange fluid from the externalsource through the circuit by means of pumping with the pump whilesimultaneously venting any gas contained in the circuit out through theair vents; and controlling the temperature of the heat exchanger fluidin the circuit by controlling the temperature of the heat generating orremoving unit.

This method may also include the step of providing a valve between theexternal fluid source and the circuit, where the valve has an openposition which permits the flow of heat exchange fluid from the externalfluid source into the circuit and a closed position which prevents theflow of heat exchange fluid from the external fluid source to thecircuit. The method may also include use of a level sensor within thecircuit to sense when the fluid level in the circuit is full, and wherethe level sensor generates a signal in response to the full fluid level.In combination with the valve, this method contemplates initiallymaintaining the valve in its open position until the sensor senses thatthe fluid level in the circuit is at an adequately full level andoperating the valve into the closed position in response to such signal.

The method of providing a temperature regulated source of heat exchangefluid can also include the step of controlling the pressure of the fluidas the fluid is circulated through the circuit. This pressure controlcan be a pressure regulator in fluid communication with the circuit, forexample a pressure damping mechanism. This pressure control can also beachieved by using a pump that is operated by an electric motor andmaintaining a predetermined current to the electric motor.

Referring to FIGS. 19A and 19B, one method of supplying heat exchangefluid to an intravascular heat exchange catheter is illustrated by fluidflow pathway, each pathway illustrating a different embodiment of thecassette of the invention. In both embodiments, fluid flows from thepump to the heat exchange catheter. The fluid returns from the catheter,passes through the external heat exchanger, and then enters a fluidreservoir. From the reservoir, the fluid moves to the pump, and thecycle repeats for the desired duration. An optional pressure regulatorcan be position in the fluid path moving from the pump to the catheter.Fluid is provided from an external fluid source, which in the embodimentof FIG. 19A enters the priming valve, and in the embodiment of FIG. 19Benters the pump head.

Examples of these methods and the respective fluid pathways are furtherunderstood by reference to FIGS. 5A and 6A. In general, this methodcomprises the steps of: (a) providing power to operate a pump head; (b)transferring fluid from an external fluid source to a chamber, (c)pumping fluid from the chamber into a pump cavity; (d) pumping fluidfrom the pump cavity to the catheter, (e) pumping fluid from thecatheter to a external heat exchanger which is positioned in heattransfer relationship with a heat generating or removing unit; (f)pumping fluid from the external heat exchanger to a heat exchange fluidreservoir, (g) pumping fluid from the heat exchange fluid reservoir intothe pump cavity; and (h) repeating steps (d) through (g) for theduration of operation of the catheter. Preferably a step for measuringthe fluid level in the heat exchange fluid reservoir is included. Suchstep can be used to insure that the reservoir remains full. Such stepcan also comprise using an optical fluid level detector to determine thefluid level, where step (h) begins when the reservoir is filled tocapacity and step (b) ceases when step (h) begins. The method forsupplying heat exchange fluid to a catheter using the embodiment of FIG.6A uses a passive-priming mechanism, while the embodiment of FIG. 5Auses a unique valved-priming mechanism, which is described in detailbelow. In the priming mechanism shown in FIG. 5A, the fluid levelmeasuring step may also comprise using an optical fluid level detectorto determine the fluid level, where step (g) begins when the reservoiris filled to capacity and step (b) ceases when step (g) begins.

Referring to the bulkhead embodiment of FIG. 6A and the flow diagram ofFIG. 19A, a method for supplying heat exchange fluid to an intravascularheat exchange catheter comprises the steps of: (a) transferring fluidfrom an external fluid source 15 to a chamber, which is the heatexchange fluid reservoir 358; (b) providing power to operate a pump head140 (c) venting air from the heat exchange fluid reservoir as the air isdisplaced by the fluid from the external fluid source; (d) pumping fluidfrom the chamber through a pump cavity 104, to a heat exchange catheter160, through an external heat exchanger 20 which is positioned in heattransfer relationship with a-heat generating or removing unit, andpumping the fluid and air displaced by the circulating fluid from theexternal heat exchanger 20 to the heat exchange fluid reservoir 358; (e)venting the air displaced by the circulating heat exchange fluid fromthe heat exchange fluid reservoir; (f) repeating steps (a) through (e)for the duration of operation of the catheter.

More particularly, the embodiment of FIGS. 6 and 6A provides themechanism for passively priming the system with heat exchange fluid froman external source 15. The external fluid source is placed above thereservoir, and is connected by a fluid providing line 16 to thereservoir. The reservoir 358 has a fill port 318 from the fluidproviding line 16. Initially, with the catheter out of the patient'sbody, the pump is operated to draw heat transfer fluid from the externalfluid supply and circulate it through the system. The air that is in thesystem is vented through the hydrophobic air vents. When the pressure inthe system is equal to the head pressure from the external fluid source(this will happen at a level which depends on the pump pressure and theheight of the external fluid source above the reservoir) the system willessentially be in equilibrium and will cease drawing fluid from theexternal source. At this point the catheter and cassette system will beconsidered to be primed. The heat exchange catheter will generallythereafter be inserted into the patient, and as the system is operated,any fluid required to be added to the system to maintain the pressureequilibrium mentioned above will be drawn from the external source whichis in fluid communication with the reservoir through fluid providingline. Likewise, any buildup of pressure in the system due, for exampleto the heating and expanding of the system, will be relieved by fluidflowing back into the external fluid supply source 15. Because of theability of the system to react to minor expansions and contractions offluid supply, there is no need to monitor the high level of fluid, andonly redundant sensors of the low level need be incorporated into thecassette.

Referring now to the bulkhead embodiment of FIG. 5A and the flow diagramof FIG. 19B, a method for supplying heat exchange fluid to anintravascular heat exchange catheter comprises the steps of: (a)automatically operating a valve to open a fluid pathway between anexternal fluid source 15 and a chamber 90 in the feedblock section of abulkhead; (b) transferring fluid from an external fluid source 15 tochamber 90; (c) operating pump head 140 to pump fluid from the chamber90 into a pump cavity 104, through heat exchange catheter 160, throughexternal heat exchanger 20 which is positioned in heat transferrelationship with a heat generating or removing unit and to exchangefluid reservoir 58; (c) venting all air displaced by the heat exchangefluid supplied to and circulated through the system; (d) continuingsteps (a) through (c) until the fluid reservoir is full and excess airis purged from the system; (e) when the fluid reservoir is full,automatically operating a valve to close fluid communication between anexternal fluid source 15 and chamber 90; (f) continuing steps (b) and(c) for the duration of operation of the catheter. More particularly,the embodiment of FIG. 5A, with its feedblock, provides the mechanismfor automatically commencing and ceasing priming the system with heatexchange fluid from an external source 15 and for circulating fluid tothe catheter 160 in a closed circuit. The external fluid source 15 has afluid providing line 16, and the catheter has a fluid supply line 150and a fluid return line 158. The external heat exchanger 20 has an inletorifice 36 and an outlet orifice 38. A heat exchange fluid reservoir 58is connected to the external heat exchanger outlet 38. Pump 140 ispositioned in a pump cavity 104, which is connected to fluid supply line150. A chamber 90 comprises a valve 84, a fill port 18 from the fluidproviding line 16, a fluid inlet 87 from the heat exchange fluidreservoir 58, and a fluid outlet 93 to the pump 140. The valve has afirst position (FIG. 11B) whereby the fill port 18 from the fluidproviding line 16 is open and the fluid inlet 87 from the heat exchangefluid reservoir 58 is closed, and a second position (FIG. 11A) wherebythe fill port 18 from the fluid providing line 16 is closed and thefluid inlet 87 from the heat exchange fluid reservoir 58 is open. Anoptical fluid level detector detects when the heat exchange fluidreservoir 58 is filled to capacity. When the reservoir is not filled tocapacity the valve is in its first position. When the reservoir isfilled to capacity, the optical fluid level detector operates to movethe valve to its second position.

As can be seen from FIG. 19C, the direction of the fluid flow and theinclusion of many of the above described elements are optional, and maybe changed, omitted or substituted as is appropriate for the fluidsupply system desired. Any such changes, substitutions or omissions maybe made without departing from the invention as disclosed, whichinvention is circumscribed only as is established in the claims.

Referring to FIGS. 11A and 11B, the priming valve 84 is positionedwithin a central chamber 90, which has two inflow channels, an inflowchannel 86 from the fluid reservoir 58 and a filling channel 88 frominlet port 18 from the external fluid source 15. The central chamber 90also has a outflow channel 92 leading to the pump section. A filter (notshown) may be located between the reservoir and the central chamber tocatch any particulate matter that may be in the heat exchange fluid. Thechamber is fitted with a guide disc 171 to support the priming valve.The priming valve is operable to fill the closed fluid circuitcomprising the heat exchange catheter 160, the external heat exchanger20 and the bulkhead 30. It may be configured to automatically prime thesystem.

The embodiment of the priming valve illustrated in FIGS. 11A and 11B isa spool valve 84, which is comprised of a spool valve stem 94, acompressible spring 99 contained within a solid block 101, and aplurality of O-rings 91. The spool valve is operable between a firstposition (FIG. 11B) and a second position (FIG. 11A), and is controlledby a spool valve activation system 164 which is mounted on the reusablemaster control unit 186, as shown in FIG. 2. The spool valve activationsystem 164 comprises a flexible membrane 96, a push rod 98 and a linearactuator 102. The valve stem 94 is located so that its top end ispositioned immediately below the membrane 96, which can be a siliconmembrane reinforced by cloth which is deformable by a sufficient degreeto allow the valve stem to be depressed to travel between the twopositions illustrated in FIGS. 11A and 11B. A push rod 98 may depressthe valve stem 94 by pushing against the membrane 96 and thence againstthe top end of the valve stem to operate the valve. The push rod, notcontained in the cassette of this invention, may be manually triggered,or may be automatically controlled. The push rod 98 may act, for exampleby means of a linear actuator 102, which will serve to exert downwardpressure on the push rod, as in FIG. 11B or will be in a releasedposition, as in FIG. 11A such that no downward pressure is exerted onthe spool valve stem 94.

The invention also encompasses a method for automatically commencing andceasing the priming of a heat exchange fluid supply system for supplyinga heat exchange fluid from an external fluid source 15 to anintravascular heat exchange catheter 160, using the means describedabove. This method comprises the steps of: (a) first providing power tooperate the pump, wherein the reservoir is not filled to capacity andthe valve is in its first position and the pump 140 operates to pumpfluid: (i) from the external fluid source 15 through the fluid providingline 16 into the fill port 18 of the chamber 90 and out of the fluidoutlet 93 into the pump cavity 104; (ii) from the pump cavity 104 tosaid fluid return line 158 to the catheter 160; (iii) from the catheter160 through the fluid supply line 150 to the external heat exchangerinlet orifice 36; (iv) from the external heat exchanger outlet orifice38 to the heat exchange fluid reservoir 58; and (v) into the heatexchange fluid reservoir 58 to fill the reservoir, (b) then filling thereservoir to capacity; at which point (c) the optical fluid leveldetector operates to move the valve to its second position and the pump140 operates to pump fluid from the heat exchange fluid reservoir 58 tothe fluid inlet 87 of the chamber 90 and out of the fluid outlet 93 intothe pump cavity 104.

When the disposable cassette of the invention is first put intooperation, the cassette 10 is initially filled with heat exchange fluidand an external fluid source such as an IV bag of saline is attached tothe filling channel 88. In addition, the linear actuator 102 isactivated, and the spool valve stem 94 is in its first position (FIG.11B, the valve stem depressed and the valve in the auto-prep position),depressed sufficiently to allow fluid to flow from the IV bag into thecentral chamber 90. In particular, the filling channel 88 is open to theoutflow channel 92 and the inflow channel 86 is closed, which allows theheat exchange fluid to flow from the external fluid supply source 15into the chamber 90 and then onto the pump section 100.

When the pump head 140 is active, heat exchange fluid is initiallypumped from the external fluid source 15 in to the chamber 90, thenthrough the catheter 160, returning to the bulkhead 30 and then onto theexternal heat exchanger 20, and from there into the reservoir 58, aswould be the case where the system was initially primed. As part of thisprocess, air is expelled through the hydrophobic vents and the reservoirbegins to fill with heat exchange fluid. The fluid level in thereservoir rises since fluid is unable to move through outlet channel 62and inflow channel 86, which is closed due to the position of the spoolvalve.

The reservoir section is provided with a means to detect when the fluidreservoir is full, as described above, whereby signals are provided tothe reusable master control unit that represent or correspond to thelevel of the heat exchange fluid in the reservoir. Using the datarepresenting the fluid level, the reusable master control unit adjuststhe linear actuator so that the position of the spool valve changes andthe fluid flow path is altered. Thus when the fluid level in thereservoir 58 rises to a sufficient level, a signal is sent to thereusable master control unit to deactivate the linear actuator 102 sothat it moves to a released position and thus withdrawing the push rod98, resulting in the spool valve stem 94 being in its second position(FIG. 11A, the valve stem relaxed and the valve in the normal operatingposition). In this second position, the inflow channel 86 is open to theoutflow channel 92 and the filling channel 88 to the external fluidsource is closed. Thus, fluid from the now full reservoir is directedfrom inflow channel 86 to outflow channel 92 and then onto the pumpsection, while fluid flow from the external fluid source is diminishedor ceases entirely.

The valve is biased into the up position, that is the position thatseals the filling channel 88, and opens the inflow channel 86. In apreferred embodiment the pump would continue to run for a period of timeafter the level sensor indicated that the system was full to ensure thatany air bubbles in the catheter or the external heat exchanger or thebulkhead would be expelled into the reservoir 58 where they could ventto the atmosphere. Since the fluid is being drawn from the bottom of thereservoir through reservoir outlet channel 62, and air moves up towardsthe top of the reservoir where the hydrophobic vents are located, thisacts to purge air from the system. Therefore, it is important to realizethat the spool valve may also have a third position that is anintermediate position from its first and second positions describedabove. In this manner, heat exchange fluid may enter the central chamber90 from either the reservoir or the external fluid source, or bothsimultaneously if the valve stem 94 is opened to this intermediateposition. So, for example, in an embodiment of the intention thatutilizes the pump in a first, intermediate and then second position,fluid would enter the pump solely from the external fluid source 15(first position, FIG. 11B), then fluid would enter the pump in part fromthe external fluid source 15 and in part from the reservoir 58(intermediate position) and finally fluid would enter the pump solelyfrom the reservoir 58 (second position, FIG. 11A).

The method for automatically commencing and ceasing the priming canfurther comprises continuously supplying the heat exchange fluid fromthe pump to the catheter 160, by repeating steps (a)(ii) to (a)(v) andstep (c)(i) for the duration of operation of the catheter, which can beto 72 hours.

The pump section is readily adapted for use with the reservoir section40 and feedblock section 80 of the cassette of FIG. 3 or the reservoirsection 340 of the cassette of FIG. 4 and is configured to allow forpumping of heat exchange fluid at a constant pressure. In thisembodiment of the invention, the pumping mechanism creates rapid flow ina heat exchange fluid supply system for supplying a heat exchange fluidto an intravascular heat exchange catheter, and comprises a cavityhaving a quasi-cardioid shape, an inlet to the cavity, an outlet fromthe cavity, a pump head comprising a rotor having a central groove, anda vane slidably mounted in the groove and impinging on the edge of thecavity.

This is illustrated in FIGS. 9 and 12A, where the pump section 100contains a cavity 104 of quasi-cardioid shape and the pump head 140. Thepump head has a rotor 106 which is circular and rotates within thecavity 104, and has a central groove 108 across the entire center of therotor. A vane 110 is slidably mounted in the groove and impinges on theedge of the cavity 104. As the rotor 106 rotates around its center, thevane 110 moves freely, sliding back and forth within the groove 108,with the ends of the vane 120, 122 being continuously in contact withthe edge of the cavity 104.

A fluid inlet channel 112 leads from the feedblock section 80 and opensinto the cavity 104 just beyond the edge of the rotor 106. A fluidoutlet channel 114 opens into the cavity 104 on the opposite side of therotor 106 and leads to the feedblock section 80. As the rotor 106rotates, the vane 120 is in continuous contact with the cavity wall 123in relatively fluid tight contact. Fluid enters into the cavity 104 fromthe inlet channel 112 and is contained in the cavity between the cavitywall 123, the rotor wall 124 and the vane 110. As the rotor 106 rotatesthe vane also moves. This causes the fluid path to increase in area asit is filled with heat exchange fluid from the inlet channel 112, andthen decrease in area as the vane pushes the heat exchange fluid throughoutlet channel 114. The rotor wall 124 is in relatively fluid tightcontact with the wall of the cavity along arc 116 and therefore fluidcannot travel directly from the inlet channel 112 to the outlet channel114 of the pump. As the rotor rotates, fluid is pumped from the inletchannel 112 around the quasi-cardioid shaped cavity and pushed by thevane out the outlet 20 channel 114. The configuration of the fluid pathcan be likened to a “crescent” shape, as can be seen in FIG. 12A.

The pump is designed to rotate within the range of 200-1000 rpm and tofunction for up to 72 hours. The choice of materials should be selectedto accommodate these needs, and suitable materials are described below.It is an additional advantage of the curved edges 120 and 122 on thevane that the point of contact between the vane edges and the cavitywall 123 changes constantly through the rotation of the rotor and thusavoids a single wear point on the edges of the vane. This allows thevane to rub against the wall of the cavity for as long as 72 hours andyet retain a relatively fluid tight contact between the edges of thevane and the wall of the cavity. In a preferred embodiment, the vane isdesigned to fit in the cavity 104 at room temperature with a slightclearance, for example 0.005 inches. This clearance is one means ofaccommodating the transient and steady state thermal changes that occurduring operation and allows for expansion of the vane due to an increasein temperature during operation. In this manner, at the temperaturesthat are encountered during normal operation, the ends of the vane 120,122 will maintain adequate contact with the wall 123 of the cavity 104for pumping.

There are numerous other vane designs that also accommodate thermalchanges so that the vane remains in continuous contact with the wall ofthe cavity and is able to move smoothly within the cavity. FIGS. 20A,20B and 20C are side views of examples of such designs. In FIG. 20A, thevane 181 is configured with cut-out sections 173, 175, which allow forexpansion or contraction of the vane during operation. In FIG. 20B, thevane 182 is configured with a center section 177 made of a compressiblematerial to accommodate expansion or contraction of the end portions 179during operation. In FIG. 20C, the vane 183 is configured with a centerspring 211 to bias the end portions 209 outward during operation tocontact the wall of the cavity regardless of the temperature of thevane.

One embodiment of the invention relates to the geometry of thequasi-cardioid shaped cavity 104 having a circumference and an inlet 112and an outlet 114 thereto, that is part of the pumping mechanism of thedisposable cassette 10, which cassette is also comprised of a pump head140 comprising a rotor 106 having a central groove 108 and a diameter“D”, and a vane 110 having length “L” slidably mounted in the groove andimpinging on the edge of the cavity. As shown in FIG. 12B, thecircumference of the cavity has four arcs, where the radius “R” or eacharc has its center at the center of the rotor 106 and is measured to thecavity wall 123.

The four arcs 116, 117, 118 and 119 are as follows: (a) a first arcdefined as 330° to 30° and having a radius R₁, (b) a second arc definedas 150° to 210° and having a radius R₂, (b) a third arc defined as 30°to 150° and having a radius R₃, and (d) a fourth arc defined as 210° to330° and having a radius R₄. These measurements are based upon thecenter of the rotor and 0° is identified with the point midway betweenthe inlet and the outlet of the cavity, i.e., the line projected fromthe center of the rotor 106 and the point on the cavity wall that ismidway between the inlet channel 112 and the outlet channel 114 isdesignated as the base line, from which 0-360° angles are measured, in aclockwise fashion. The four radii are defined as follows:R ₁ =D/2R ₂ =L−(D/2)R ₃=(D/2)+{[(L−D)/2]·[cos(1.5θ+135)]}R ₄=(D/2)+{[(L−D)/2]·[cos(1.5θ−315)]}

Therefore, arc 116 (330° to 30°) is circular and thus has a constantradius, designated R₁; arc 117 (30° to 150°) is not circular since itsradius changes as the angle of rotation (designated “θ”) increases from30° to 150°, and is designated R₃; arc 118 (150° to 210°) is alsocicular and thus also has a constant radius, designated R₂; and arc 119(210° to 330°) is not circular since its radius changes as the angle ofrotation decreases from 210° to 330°, and is designated R₄. Thesecalculations are somewhat approximate because the vane has width, andthe end of the vane also has a radius (i.e. is curved) and the exactcontact point between the vane and the wall of the cavity variesslightly with the rotation of the rotor. Since both ends of the vanehave the same radius of curvature, this is equal on each side, and theexact shape of the cardioid cavity can be adjusted to compensate forthis slight variance and still maintain contact at all points betweenthe vane and the cavity wall.

Turning to FIG. 13, the rotor 106 of the pump head is made of a rigidand durable material with adequate lubricity to sustain a long period ofclose contact with the cavity wall 123 while rotating without unduewear. The rotor 106 may be made of, for example, polyvinylidenefluoride, and the vane 120 may be made of a material such as highdensity polyethylene. The rotor is mounted on a shaft 128 by means of apin 129 and has a seal 130 and a bearing 132 separated by an optionalspacer 131, provided in a manner known to those of skill in the art ofrotating shafts mounted in fluid-tight arrangement.

The shaft 128 protrudes below the rotor 106 and is fitted with threewheels 134, 136 and 138 which cooperate with a pump drive mechanism 184housed in the reusable master control unit 186, which imparts rotationalmotion to the shaft and thence to the rotor. The top most wheel 134 is asmooth alignment wheel, the middle wheel 136 is a toothed drive wheel,and the bottom most wheel 138 is another smooth alignment wheel. Thedrive wheel 136 can be constructed, for example, of a plastic materialsuch as nylon or polyurethane. The alignment wheels 134 and 138 can beconstructed, for example, of a polycarbonate material. These threewheels cooperate with a plurality of wheels on the reusable mastercontrol unit 186, two of which are depicted in FIG. 2 as guide wheels190 and 192. A toothed motor wheel 188 is driven by the pump drivemechanism 184, and is shown in FIGS. 14 and 15, which depict placementof the pump wheels 134, 136 and 138 within the control unit 186. FIGS. 2and 14 also shows placement of the gear shield 19, which covers theopening in the control unit 186 once the cassette 10 is positioned inplace.

When the cassette 10 is inserted into the reusable master control unit186, the toothed drive wheel 136 engages the toothed portion 189 ofmotor wheel 188. The drive wheel 136 and motor wheel 188 are held insnug juxtaposition by contact between guide wheels 190, 192 andalignment wheels 134, 138, respectively. As can be seen in FIG. 15, theguide wheels have a larger diameter top 191 and bottom 193 section, witha small diameter middle section 195. This allows the top 191 to fitsnugly against alignment wheel 134 and the bottom 193 to fit snuglyagainst alignment wheel 138, while at the same time the middle section195 will not come in to contact with the toothed drive wheel 136. Theguide wheels can be machined as a single spool-shaped unit or the top,middle and bottom sections can be separate pieces that are permanentlyaffixed together. The toothed motor wheel can also be designed to have aslightly larger top section 207 that fits snugly against alignment wheel134 and/or a slightly larger bottom section 208 that fits snugly againstalignment wheel 138. Preferably the motor wheel makes contact with atleast one of the smooth alignment wheels.

The positioning of the alignment and guide wheels causes the teeth ofmotor wheel 188 and drive wheel 136 to engage at the appropriatedistance so that the teeth are not forced tightly together. The diameterof the smooth alignment wheels 134, 138 will be approximately the pitchdiameter of the drive wheel 136 to provide proper positioning of thedrive teeth. Similarly, the diameter of the top and bottom sections,207, 208, of the motor wheel 188 will be approximately the pitchdiameter of the toothed portion 189 of the motor wheel 188. This isadvantageous in imparting smooth rotation motion without imparting sideforces to the drive shaft, or causing friction between the teeth byvirtue of their being jammed together.

The diametral pitch of the drive wheel 136 and the motor wheel 188 arethe same; however they will typically have different diameters. Forexample, a suitable diametral pitch is 48 (48 teeth per inch indiameter), which has been found to provide adequate strength withminimal noise during operation. A typical drive wheel 136 will have apitch diameter of 1″, while the corresponding motor wheel 189 will havea pitch diameter of about ⅜″.

The pump is designed to operate for significant periods of time, forexample in excess of 72 hours, at fairly high rotational speeds, forexample approximately 800 rpm, and to operate to pump fluids oftemperature that vary between approximately 0° C. and 45° C. It isdesirable that the heat exchange catheter is supplied with fluid at arelatively constant pressure at the inlet to the catheter, for exampleabout 40-46 psi, but wear and temperature variations may affect theoutput pressure of the pump. In the embodiment which includes thepressure regulator, the pump is designed to have an output pressureslightly higher than the optimal pressure for the heat exchangecatheter, for example 42-48 psi, and the pressure is regulated down tothe desirable pressure of 40-46 psi. If the output pressure of the pumpvaries, the pressure regulator can be incorporated into the disposableheat exchange supply cassette 10 to ensure that the heat exchangecatheter is provided heat transfer fluid at a relatively constantpressure. The pressure regulator can be, for example, a pressureregulator valve or a pressure damper used with a constant current supplyin the disposable heat exchange supply cassette 310.

A preferred pressure regulator valve is described here, but it may bereadily perceived that one of ordinary skill may substitute anyappropriate pressure regulator valve for this function. In the preferredembodiment of the pressure regulator valve shown in FIG. 16, the outlet114 of the pump is fluidly connected to the inlet of the pressureregulator chamber 198 by means of channel 196. The pressure of the fluidat the pump output may vary somewhat depending on wear and fluidtemperature, and may be, for example, 45-54 psi.

A pressure regulator shaft 200 is mounted in the fluid reservoir 58through the mounting block 75. This may be in the form of a shaft withscrew threads mounted in a hole 194 in the block with mating screwthreads. A reference spring 202 is mounted between the shaft 200 and adiaphragm 204. The diaphragm may be a membrane, for example, a clothreinforced silicone membrane. The pressure on the reservoir side of thediaphragm is the pressure of the fluid in the reservoir 58, which byvirtue of the hydrophobic gas permeable vents 54 is essentiallyatmospheric pressure, plus the pressure applied by reference spring 202.The pressure of reference spring 202 may be adjusted by turning theshaft in the hole and thus tightening or loosening the spring againstthe diaphragm. A pressure block 206 is attached between the diaphragm204 and the reference screw 202 to apply distribute the pressure of thespring to the reservoir side of diaphragm 204.

On the other side of the diaphragm 204 a push rod 210 is attached. Thepush rod 210 extends through a throttle chamber 212. The throttlechamber 212 has a cloverleaf cross sectional configuration in the formof a central throttle aperture 216 surrounded by four lobes 214, as maybest be seen in FIG. 17. The end of the push rod 210 distal of thediaphragm 204 extends to the end of the throttle chamber 212 to throttleaperture 218. A counter spring block 220 is mounted across the face ofthe aperture 218 and is biased toward the aperture by means counterspring 222. This counter-spring block 220 may seal down against the openaperture 218 to create a fluid-tight seal between the sensing chamber224 and the regulator chamber 198. Alternatively, if the pressureapplied against the diaphragm by the spring 202 and the pressure in thereservoir 58 is sufficient to deform the diaphragm inward toward thesensing chamber 224, the push rod 210 forces the counter-spring block220 away from the throttle aperture 218 and thus opens a throttle gapthrough which fluid may flow between the regulator chamber 198 and thesensing chamber 224. Because the throttle gap is relatively narrow,there is a pressure drop as fluid flows through the throttle gap. Inpractice, the reference spring 202 is adjusted so that the pressureagainst the diaphragm 204 and thus against the push rod 210 is about 43psi. When the pressure in the regulator reservoir 198 is greater than 43psi, it forces the counter spring block 220 closer to the throttleaperture 218 thus narrowing the throttle gap. This functions toautomatically adjust the throttle gap so that the pressure drop acrossthe throttle gap is the same as the excess pressure between the fluid inthe regulator reservoir 198 and the pressure set by the reference spring202 against the diaphragm 204, generally 43 psi. This acts to regulatethe pressure of the fluid in the sensing chamber 224 to 43 psi. Thefluid exits the sensing chamber through outlet 220 and thence to fluidsupply line 150 to the catheter. In this way fluid at a relativelyconstant pressure is supplied to the catheter. It may also be seen thatsuch a pressure regulator may function to damp any pressure variations,such as vibrations in the fluid line generated by the pump. For suchuses, a regulator as described herein may be adequate. Other pressureregulators, as are well known in the art, will also suffice forregulating pressure of the pumped fluid, including systems forcontrolling other flow characteristics such as dampening vibrations.

In operation, the rotor 106, including vane 110, is rotating at asufficiently constant rate to generate relatively constant pressure.However, due to the shape of the cavity 104, a variable pressure can beimparted to the fluid being moved by the vane, resulting in pressurefluctuations or uneven fluid flow in the fluid flowing from thefeedblock section 80 to the catheter through fluid supply line 150.These pressure fluctuations or uneven fluid flow may cause undesirablevibration of the catheter through which the fluid is flowing. In theembodiment described in FIG. 5, the pressure regulator serves toeliminate undesirable pressure fluctuations.

However, it may be desirable to eliminate the pressure regulator valve,pressure regulator chamber and sensing chamber from the cassette design.In that instance, another means of insuring constant pressure andproviding for smooth fluid flow can be incorporated into the cassettedesign.

The pump drive mechanism 184 typically comprises an electric motor and apower supply that provides the necessary current to run the motor.Constant current can be attained by directing the voltage from the powersupply to an amplifier which adjusts and controls the fluctuatingvoltage input to provide a constant current output to the motor. With aconstant current supplied to the electric motor that runs the pump, themotor provides for constant torque to the pump head 140, whichultimately provides for constant pressure supplied to the catheter 160.

Accordingly, in one embodiment of the disposable cassette of theinvention, the cassette comprises an external heat exchanger having aninlet and an outlet, a first fluid supply line in fluid communicationwith the heat exchanger inlet, a disposable pump head having a pumpinlet in fluid communication with the heat exchanger outlet and having apump outlet, a second fluid supply line in fluid communication with thepump outlet for receiving fluid pumped out of the pump outlet, and anoptional pressure regulator in fluid communication with the pump outletfor regulating the pressure of fluid pumped from the pump head. The pumphead is actuated by an electric motor that is controlled by an amplifiercontroller, where the amplifier controller supplies a constant currentto the pump head thereby causing the pump head to supply a relativelyconstant pressure to the fluid in the second fluid supply line.

In another embodiment of the invention, the cassette comprises: (a) anexternal heat exchanger comprising a structural member and a compliantmember, where the compliant member is sealed to the structural member ina pattern that forms a flow channel between the compliant member and thestructural member, and where the flow channel has an inlet and anoutlet; (b) a first fluid supply line in fluid communication with theflow channel inlet; (c) a bulkhead comprising a reservoir and adisposable pump head, where the reservoir contains an inlet in fluidcommunication with the flow channel outlet, and further has a fluidlevel detector for detecting the level of fluid within the reservoir,wherein the pump head is a cardioid vane pump head having an inlet andan outlet, and the pump head is actuated by an electric motor, where thepump inlet is in fluid communication with the reservoir outlet and theelectric motor is controlled by an amplifier controller, where theamplifier controller supplies a constant current to the pump headthereby causing the pump head to supply a relatively constant pressureto the fluid in the second fluid supply line; (d) a second fluid supplyline in fluid communication with the pump outlet for receiving fluidpumped out of the pump outlet; (e) an external fluid source in fluidcommunication with the reservoir, and (f) a pressure damper in fluidcommunication with the pump outlet.

One embodiment for providing smooth fluid flow is illustrated in FIG.18, which is a cross-sectional view of a pressure damper, that may beused in place of the pressure regulator components. In this embodimentof the invention, a pressure damper is included in a heat exchange fluidsupply system for supplying a heat exchange fluid to an intravascularheat exchange catheter where the heat exchange fluid supply system has areservoir section, a feedblock section and a pump section, wherein thepressure damper comprises a pressure dampening chamber filled with acompressible material housed in the feedblock section, adjacent to aflow-through channel having an inlet which leads from the pump and anoutlet which leads to the catheter. The compressible material ispreferably air tight. Suitable examples include a block of foam,encapsulated foam such as polyethylene foam encased in a polyethylenefilm, foam enclosed within a sealed plastic pouch, foam coated with orimpregnated with plastic or silicone, gas encapsulated within a flexiblepouch such as a polyethylene balloon, and so forth.

Referring to FIG. 18, a pressure dampening chamber 230 is positionedadjacent to and in fluid flow communication with the fluid flowing fromthe pump in the pump outlet channel 314 towards the outlet channel 319.As can be seen in FIG. 18, the dampening chamber need not be positioneddirectly in the fluid flow path. The chamber must simply be in aposition such that it is in contact with fluid being pumped from thepump through channel 314. The chamber 230 is partially filled with acompressible material 232. As fluid contacts the compressible material232, the material compresses slightly and then returns to its originalconfiguration, and in doing so acts as a cushion to absorb minorpressure fluctuations uneveness of the fluid flow. This compressiblematerial movement thus has the effect of smoothening the fluid flow.

The external heat exchanger 20 is attached to the bulkhead 30 orbulkhead 330 by means of a mechanical seal formed when the external heatexchanger is attached over the bulkhead and a cover plate shown as coverplate 168 in FIG. 3 and as cover plate 368 in FIG. 4. The cover plate isattached over the external heat exchanger and attached to the bulkhead,trapping the extended attachment 48 of the external heat exchangerbetween the cover plate and the bulkhead. Referring to the embodiment ofFIG. 3, the cover plate is formed with a handle 170, a vent aperture 172that is located over and seal the periphery of the hydrophobic gaspermeable vents. 54 to allow any air present in the fluid reservoir 58to vent to the atmosphere. The cover plate is also formed with a primingvalve aperture 174 that provides access to the cover of the primingvalve 84, for example so that push rod 98 is able to contact theflexible membrane 96 and depress the valve stem 94 during the automaticpriming sequence described above. Located on the bottom of the coverplate 168 are two circular recessed areas (not shown), a first recess178 that fits over and seals the priming valve 84 and a second recess180, containing an O-ring 182 that fits over and seals cavity 104. Thebottom of the cover plate may have one or more straight recessed areasinto which a portion of the fluid lines such as lines 16, 150, 158 maybe positioned. The cover plate may be secured to the bulkhead by anysuitable means, for example by a plurality of suitably positionedhex-headed screws 176.

The cover plate is also configured to have one or more means forindicating to the user that the cassette is in the correct position foroperation. For example, the cover plate may have a slot that operates todepress a switch on the control unit to indicate proper placement.Similarly, the cover plate may have slots 199 and 201, withcorresponding depressions 203 and 205, which correspond to bearings onthe control unit. When the cassette is being positioned within thecontrol unit, the bearings will move along the slots 199 and 201 andonce the cassette is completely in place, the bearings will move intodepressions 203 and 205, with an audible click to inform the user thatplacement is complete.

Cover plates 168 and 368 are configured in a similar manner, with theexception that cover plate 368 does not have a priming valve aperture174 or first recess 178 since the embodiment of FIG. 4 does not have apriming valve.

Referring back to FIGS. 1 and 2, the disposable fluid supply cassette 10of the invention is shown as being attached to a heat exchange catheter160, external fluid source 15 and positioned in cooperation with asuitable reusable master control unit 186. Prior to commencingtreatment, the cassette is inserted into the reusable master controlunit, the external fluid source is attached to the fill port and thepump is automatically or passively primed and filled, after which thecatheter is ready for insertion in the vasculature of the patient, forexample in the inferior vena cava or the carotid artery. Chilled orwarmed biocompatible fluid such as saline, is pumped into the closedcircuit catheter, which exchanges heat directly with the patient'sblood. The control unit serves to automatically control the patient'stemperature. Once treatment with the catheter is complete, the catheteris removed from the patient and the cassette is removed from thereusable master control unit. Both the catheter and cassette are thendiscarded. The reusable master control unit, however, which never comesinto direct contact with the heat exchange fluid, is ready for immediateuse for treatment on other patients, along with a new cassette andcatheter and fresh external fluid source.

Each of the patents, publications, and other published documentsmentioned or referred to in this specification is herein incorporated byreference in its entirety.

While the present invention has been described with reference to thespecific embodiments thereof, it should be understood by those skilledin the art that various changes may be made and equivalents may besubstituted without departing from the scope of the invention. Inaddition, many modifications may be made to adapt a particularsituation, material, composition of matter, process, process step orsteps, while remaining within the scope of the present invention.Accordingly, the scope of the invention should therefore be determinedwith reference to the appended claims, along with the full range ofequivalents to which those claims are entitled.

1. A disposable cassette for supplying a heat exchange fluid to a heatexchange catheter, said cassette comprising: an external heat exchangercomprising a flow channel having an inlet and an outlet, the externalheat exchanger also having a structural member and a compliant member,said compliant member being sealed to said structural member in apattern, said pattern forming the flow channel between said compliantmember and said structural member; a first fluid supply line, said firstfluid supply line in fluid communication with said flow channel inlet; apump head contained in the disposable fluid supply cassette, said pumphead having a pump inlet and a pump outlet, said pump inlet in fluidcommunication with said external heat exchanger flow channel outlet forpumping fluid from said flow channel outlet; a second fluid supply line,said second fluid supply line in fluid communication with said pumpoutlet for receiving fluid pumped out of said pump outlet; and apressure regulator, said pressure regulator in fluid communication withsaid pump outlet for regulating the pressure of fluid pumped from saidpump; and an external fluid source in fluid communication with the pumpfor priming the pump.
 2. The cassette of claim 1 wherein first andsecond fluid supply lines are connected through a heat exchange catheterthereby creating a fluid circuit including said external heat exchanger,said pump, said first and second fluid lines, and said catheter.
 3. Thecassette of claim 1 wherein said pressure regulator is a regulatorvalve.
 4. The cassette of claim 3 wherein said pressure regulatorfurther comprises a pressure regulator chamber adjacent to a sensingchamber which communicates with the pressure regulator valve.
 5. Thecassette of claim 4 wherein said pressure regulator chamber comprises acounter spring and a counter spring block.
 6. The cassette of claim 4wherein said sensing chamber comprises a diaphragm and push rod.
 7. Thecassette of claim 1 wherein said pressure regulator is a pressuredamper.
 8. The cassette of claim 7 wherein said pressure damper is acompressible material.
 9. The cassette of claim 8 wherein saidcompressible material is a gas encapsulated within a flexible pouch. 10.The cassette of claim 8 wherein said compressible material is a block offoam.
 11. The cassette of claim 10 wherein said foam is enclosed with asealed plastic pouch.
 12. The cassette of claim 10 wherein said foam iscoated with plastic or silicone.
 13. A disposable cassette for supplyinga heat exchange fluid to a heat exchange catheter, said cassettecomprising: an external heat exchanger comprising a flow channel havingan inlet and an outlet; a first fluid supply line, said first fluidsupply line in fluid communication with said flow channel inlet; a pumphead contained in the disposable fluid supply cassette, said pump headhaving a pump inlet and a pump outlet, said pump inlet in fluidcommunication with said external heat exchanger flow channel outlet forpumping fluid from said flow channel outlet; a second fluid supply line,said second fluid supply line in fluid communication with said pumpoutlet for receiving fluid pumped out of said pump outlet; a pressureregulator including a regulator valve and a pressure regulator chamberlocated adjacent a sensing chamber which communicates with the pressureregulator valve, said pressure regulator in fluid communication withsaid pump outlet for continuously regulating the pressure of fluidpumped from said pump; and an external fluid source in fluidcommunication with the pump head to prime the pump head.